Quantifying lymphocyte receptor diversity

TL;DR

This paper reviews recent modeling approaches for quantifying lymphocyte receptor diversity from sequencing data, highlighting the challenges and biological relevance of different diversity measures.

Contribution

It clarifies various notions of diversity, discusses inference methods, and emphasizes the importance of functional diversity over sequence diversity.

Findings

Different mathematical indices of diversity are compared.

Inference methods for receptor diversity are described.

Limitations of sequence-based diversity measures are discussed.

Abstract

To recognize pathogens, B and T lymphocytes are endowed with a wide repertoire of receptors generated stochastically by V(D)J recombination. Measuring and estimating the diversity of these receptors is of great importance for understanding adaptive immunity. In this chapter we review recent modeling approaches for analyzing receptor diversity from high-throughput sequencing data. We first clarify the various existing notions of diversity, with its many competing mathematical indices, and the different biological levels at which it can be evaluated. We then describe inference methods for characterizing the statistical diversity of receptors at different stages of their history: generation, selection and somatic evolution. We discuss the intrinsic difficulty of estimating the diversity of receptors realized in a given individual from incomplete samples. Finally, we emphasize the limitations of diversity defined at the level of receptor sequences, and advocate the more relevant notion of functional diversity relative to the set of recognized antigens.